PB1929: EFFICACY AND SAFETY OF ACALABRUTINIB IN CHINESE PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA: AN OPEN-LABEL, MULTICENTER PHASE 1/2 TRIAL
Authors: Shenmiao Yang, Haiwen Huang, Keshu Zhou, Xielan Zhao, Yan-Qiu Han#, Lindong LI, Anna Butturini, Yiqiu Wang, Xiaofeng Liu, Peiqiong Lai, Jianyong LI
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Acalabrutinib (acala), a selective next-generation covalent Bruton tyrosine kinase inhibitor with minimal off-target activity, is approved in the United States and Europe for the treatment of chronic lymphocytic leukemia (CLL). The primary studies supporting the approval of acala in CLL were conducted predominantly in Europe and North America, with limited representation of Asian populations. This phase 1/2 study (NCT03932331) evaluated acala in Chinese patients (pts) with relapsed/refractory (R/R) CLL. Aims: To evaluate the clinical efficacy and safety of acala in Chinese pts with R/R CLL. Methods: Adults with active CLL, Eastern Cooperative Oncology Group (ECOG) performance status of ≤2, who received ≥1 prior systemic therapies for CLL were enrolled to received acala 100 mg twice daily in 28-d cycles until disease progression or treatment discontinuation for another reason. The primary endpoint was overall response rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia criteria as assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR) and progression-free survival (PFS) as assessed by BICR; ORR, DOR, and PFS as assessed by investigators (INV); overall survival (OS); and adverse events (AEs). Results: In total, 60 pts from 20 sites in China received acala (median age 62 y; 68.3% male; 21.7% del(17p) and/or TP53 mutation; median 1 prior therapy). At the data cutoff of June 28, 2022, 53 pts (88.3%) were receiving acala; reasons for acala discontinuation were progressive disease (5.0%), AEs (3.3%), patient decision (1.7%), and other (1.7%). Median duration of treatment was 13.9 (range 0.6–22.4) mo. ORR by BICR was 83.3% (95% CI 71.5, 91.7); no pt had complete response (CR). Median DOR by BICR was not reached (NR). At a median follow-up of 14.4 mo, median PFS by BICR was NR; the estimated 12-mo PFS rate was 90.7% (95% CI 78.9, 96.0). When assessed by INV, ORR was 76.7% (95% CI 64.0, 86.6) with 1 pt having CR, median DOR was NR, and median PFS was NR with an estimated 12-mo PFS rate of 94.9% (95% CI 84.9, 98.3). Median OS was also NR; the estimated 12-mo OS rate was 96.7% (95% CI 87.3, 99.2). AEs of any grade were reported in 58 pts (96.7%); 25 pts (41.7%) had grade ≥3 AEs, most commonly decreased neutrophil count (13.3%, n=8) and upper respiratory tract infection (6.7%, n=4) (Table). AEs leading to treatment discontinuation included paraneoplastic pemphigus (n=1) and rectal neoplasm (n=1). Nine pts (15.0%) had serious AEs (SAEs); only 1 SAE occurred in >1 pt (pneumonia, n=2). Fatal AEs (occurring ≤30 days after last dose) were reported in 1 pt (cardiac arrest in a 73-year-old patient with multiple cardiorespiratory comorbidities on study day 34). Among events of clinical interest, hypertension was reported in 3 pts (5.0%). There were no cases of atrial fibrillation/flutter, major hemorrhage, interstitial lung disease/pneumonitis, second primary malignancies, or tumor lysis syndrome. Summary/Conclusion: This is the first study to evaluate acala efficacy and safety in a Chinese R/R CLL population. Acala demonstrated a high ORR with durable responses. Efficacy results were similar to those of the pivotal, global ASCEND trial in a predominantly Caucasian population with R/R CLL (Ghia P et al. J Clin Oncol. 2020;38:2849-61). Acalabrutinib was well tolerated; reported AEs were consistent with the known safety profile of acala. No unexpected safety observations were observed in Chinese patients with R/R CLL.Keywords: Phase I/II, Chronic lymphocytic leukemia, Clinical trial